How to Rationally Identify Promising Cancer Chemoprevention Agents

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 How to Rationally Identify Promising Cancer Chemoprevention Agents

There is no doubt that risk of many cancers is to a large extent modifiable. Not smoking will prevent a large number of human cancers, and vaccination for HPV infection protects against cervical and oropharyngeal cancers. Landmark migrant studies showed that moving from Japan to the United States reduced the risk of stomach cancer while increasing the risk of cancers of the breast, colon, and prostate. Results of epidemiological studies are strongly suggestive that certain micronutrients and food consumption patterns may prevent several cancer types. However, the results of randomized phase III trials testing these notions have been mostly disappointing, and some studies have even indicated harm.

Interfering with hormone action has provided a mechanism-based rationale for several phase III chemoprevention trials with antiestrogenic drugs for breast cancer and with 5α-reductase inhibitors for prostate cancer. While these studies have indicated efficacy of these agents, benefit may be restricted to certain cancer subtypes and side effects can occur. Antiestrogenic treatments are only indicated for women to prevent a second primary breast cancer and for women at high risk of a first breast cancer (1). However, antiestrogenic interventions are not generally used for the prevention of primary breast cancer (2,3), and the US Food and Drug Administration has not approved 5α-reductase inhibitors for the prevention of prostate cancer (4,5). Currently, there are no interventions with drugs or micronutrients for chemoprevention of primary cancers in the general population. It is thus …(Note: to read further requires $$)

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Article: Predictive Value Tools as an Aid in Chemopreventive Agent Development JNCI J Natl Cancer Inst (2015) 107 (12): djv259 doi:10.1093/jnci/djv259 
• Abstract
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 Background: Over 25 years, the National Cancer Institute’s Division of Cancer Prevention has entered some 800 agents into a chemopreventive agent testing program. Two critical steps involve: 1) in vitro/in vivo morphologic assays and 2) animal tumor assays (incidence/multiplicity reduction). We sought to determine how accurately the earlier-stage (morphologic) assays predict efficacy in the later-stage (animal tumor) assays.....